This study proposed to explore the biochemical pathogenesis of the renal tubular dysfunction secondary to trace metal intoxication, particularly cadmium. Investigations will be performed on experimental animals (rats) chronically exposed to an excess of the trace metal. When renal tubular abnormalities appear, the kidneys will be removed and examined by electron microscopy, by atomic absorption spectrophotometry for trace metal analysis (of cortex and medulla crude homogenates and subcellular fractions) and biochemically, focussing on alterations in ATP synthesis and Na-K-ATPase activity. The inter-relationship between free and protein-bound trace metal (e.g., cadmium-metallothionein) will also be examined at various stages of development of the renal tubular disorder.